Certain carboxylic acids containing a phenyl group substituted with a bis(2-chloroethyl)amino group are well-known antitumour agents.
By reaction of such acids with steroids, having readily esterifiable hydroxyl groups, carboxylic esters have been obtained which, in addition to the antitumour effect exerted by the acid part, may possess valuable hormonal activities, derived from the steroid part. Such esters are described in e.g. J. Med. Chem. 11 (1968) 1106, ibid 12 (1969) 810, ibid 15 (1972) 1158, and U.S. Pat. No. 3,732,260.
The alcohol part of the above-mentioned esters have in the past been restricted to steroids containing hydroxyl groups bound to saturated or aromatic carbon atoms.
A third and very different type of steroid esters are enol esters. It is known that such esters may be prepared through enolisation of carbonyl groups in the steroids, but, to the best of our knowledge, no such enol esters are known which in their acid part contain an alkylating group such as the bis(2-chloroethyl)amino group, neither has any such ester been suggested.
Such esters have now been prepared by us, and it has, moreover, been found that such enol esters of the present invention are highly active against animal tumours. The esters have also been found to have a remarkably low toxicity resulting in very favourable therapeutic indexes.
Depending on the nature of steroid, these compounds also show such pharmacological activities which derive from the steroids themselves, e.g., androgenic, anabolic, gestogenic, and corticoid activities. As many steroids are used in connection with treatment of cancer diseases, the steroid part of the molecule can be selected with relation to the kind of tumor which is to be treated.
The compounds of this invention are therefore of value in the treatment of tumours, especially those situated in organs, which are targets for steroid hormones.